Hornsby Peter J
Sam and Ann Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78245, USA.
Sci Aging Knowledge Environ. 2003 Jul 30;2003(30):PE21. doi: 10.1126/sageke.2003.30.pe21.
Mice and humans are at opposite ends of the mammalian spectrum of longevity. A major question in biology is whether this difference can be accounted for by differences in the properties of cells from these two species. A new publication from Judith Campisi's lab reports that human cells in culture are more resistant than mouse cells to the damaging effects of 20% oxygen. The greater burden of DNA damage sustained by mouse cells causes them to rapidly enter a phase of culture in which most cells enter permanent growth arrest (replicative senescence). However, some mouse cells usually escape from senescence and then grow into an immortal cell line. This never happens in human fibroblast cell cultures. Human cells also eventually enter replicative senescence in culture, but this phenomenon is caused by shortening of telomeres and not by DNA damage of the type responsible for mouse cell senescence. Human fibroblasts never spontaneously escape from senescence. This Perspective reviews differences between mouse and human cells that could account for these differences in behavior. Some evidence indicates that human cells are generally more resistant than mouse cells to oxidative damage to DNA, but more needs to be done to confirm this finding and to understand the underlying mechanisms. Whether or not there are differences in the amount of DNA damage caused by oxygen or in the early phase of repair, there may be important differences in the later consequences of DNA damage. Mouse cells appear to be able to continue to divide with DNA damage that has not been repaired or has been misrepaired, and becomes fixed in the form of chromosomal abnormalities. The checkpoints that cause cells to stop dividing when chromosomes develop abnormalities (aberrations or shortened telomeres) appear to operate more efficiently in human cells. Much more work is needed to understand the basis for these differences and the implications for aging and cancer.
小鼠和人类处于哺乳动物寿命谱的两端。生物学中的一个主要问题是，这种差异是否可以用这两个物种细胞特性的差异来解释。朱迪思·坎皮西实验室的一项新研究报告称，培养中的人类细胞比小鼠细胞对20%氧气的损伤作用更具抗性。小鼠细胞承受的更大DNA损伤负担导致它们迅速进入培养的一个阶段，在此阶段大多数细胞进入永久性生长停滞（复制性衰老）。然而，一些小鼠细胞通常会逃脱衰老，然后生长成永生细胞系。这种情况在人类成纤维细胞培养中从未发生过。人类细胞在培养中最终也会进入复制性衰老，但这种现象是由端粒缩短引起的，而不是由导致小鼠细胞衰老的那种DNA损伤引起的。人类成纤维细胞从不自发逃脱衰老。这篇观点文章综述了小鼠和人类细胞之间的差异，这些差异可能解释了它们在行为上的这些不同。一些证据表明，人类细胞通常比小鼠细胞对DNA的氧化损伤更具抗性，但需要更多研究来证实这一发现并理解其潜在机制。无论氧气造成的DNA损伤量或修复早期阶段是否存在差异，DNA损伤的后期后果可能存在重要差异。小鼠细胞似乎能够带着未修复或错误修复的DNA损伤继续分裂，并以染色体异常的形式固定下来。当染色体出现异常（畸变或端粒缩短）时导致细胞停止分裂的检查点在人类细胞中似乎运作得更有效。需要做更多工作来理解这些差异的基础以及对衰老和癌症的影响。
